Recent Advances in Genetics of Moyamoya Disease: Insights into the Different Pathogenic Pathways

Abstract

Moyamoya disease (MMD) is a rare yet clinically significant cerebrovascular disorder characterized by progressive stenosis of the distal internal carotid artery and/or its principal branches, accompanied by the development of characteristic collateral vessel networks. This disease demonstrates a complex multifactorial etiology with strong genetic determinants, as evidenced by its distinct geographical distribution patterns and familial clustering. Recent genetic researches have identified multiple pathogenic mutations contributing to MMD development through three principal mechanisms: progressive vascular stenosis, abnormal angiogenesis, and dysregulated inflammatory responses. Furthermore, moyamoya syndrome frequently occurs as a secondary vascular complication in various monogenic disorders. This review provides a comprehensive analysis of recent genetic advances in MMD in view of diverse pathogenic pathways, offering valuable perspectives on the molecular mechanisms underlying disease development and potential therapeutic targets.

Keywords: genetics; moyamoya disease; moyamoya syndrome; pathogenic; pathways.

Figure 1

Integrated pathophysiological network of Moyamoya disease: Molecular crosstalk across angiogenic dysregulation, epigenetic modulators, and metabolic-immune axis. Italicized text indicates relevant genes; PDGF: platelet-derived growth factor; OGFR: opioid growth factor receptor; CCL2: cell chemokine ligand 2; Ang-1/2: angiopoietin-1/2; Cav-1: caveolin-1; ICAM1: intercellular adhesion molecule 1; TGF-β: transforming growth factor β; bFGF: basic fibroblast growth factor; VEGF: vascular endothelial growth factor; NF-κB: nuclear factor κ-B; NFAT: nuclear factor of activated T-cells; TNF-α: tumor necrosis factor-α; IFN-γ: interferon-γ; NO-sGC-cGMP: nitric oxide-soluble guanylyl cyclase-cyclic guanosine monophosphate; MMPs: matrix metalloproteinases; TIMPs: tissue inhibitors of metalloproteinases.